WHO PQ Overview document

PQDx_007 v4 22 March 2011 OVERVIEW OF THE PREQUALIFICATION OF DIAGNOSTICS ASSESSMENT PROCESS Prequalification of Diagnostics D i a gn o s t i c s a n d L ab o r a t o r y T e c h n o l o g y D i a gn o s t i c s a n d L ab o r a t o r y T e c h n o l o g y PQDx_007 v4 22 March 2011 2 Table of Contents page 1. Introduction .......................................................................................................................3 2. Intended Audience .............................................................................................................3 3. Process Overview ...............................................................................................................4 3.1. About prequalification of diagnostics............................................................................... 4 3.2. Eligibility for prequalification of diagnostics..................................................................... 4 3.3. "Re-branding" arrangements ........................................................................................... 4 3.4. Prioritization criteria for the review of applications ......................................................... 5 3.5. Readiness for prequalification ......................................................................................... 5 3.6. Components of the prequalification of diagnostics assessment process ......................... 5 4. Review of an Application Form and Product Dossier............................................................6 4.1. Application form submission ........................................................................................... 6 4.2. Product dossier submission ............................................................................................. 7 5. Laboratory Evaluation of the Product..................................................................................8 6. Inspection of the Manufacturing Site(s)...............................................................................9 7. Outcome of the Prequalification Assessment ......................................................................9 8. Post-Market Surveillance of WHO Prequalified Diagnostics ............................................... 11 9. Prequalification Assessment Fee ....................................................................................... 12 10. Eligibility to Participate in WHO and other UN Procurement Processes.............................. 12 11. Notification of Variations to Prequalified Diagnostics........................................................ 12 12. Validity of Prequalification Status ..................................................................................... 13 13. Confidentiality .................................................................................................................. 13 14. Conflict of Interest ............................................................................................................ 13 15. Relevant Documents......................................................................................................... 14 15.1. Documents relevant to the application form / product dossier review .......................... 14 15.2. Documents relevant to the laboratory evaluation stage ................................................ 14 15.3. Documents relevant to the inspection of the manufacturing site(s) stage ..................... 14 16. Contact Information ......................................................................................................... 14 PQDx_007 v4 22 March 2011 3 1. Introduction The World Health Organization (WHO) Prequalification of Diagnostics Programme is coordinated through the Diagnostics and Laboratory Technology Team (DLT), in the department of Essential Health Technologies (EHT). The aim of the WHO Prequalification of Diagnostics Programme is to promote and facilitate access to safe, appropriate and affordable diagnostics of good quality in an equitable manner. Focus is placed on diagnostics for high burden diseases and their suitability for use in resource-limited settings. The WHO Prequalification of Diagnostics Programme undertakes a comprehensive assessment of the submitted products through a standardized procedure which is based on WHO prequalification requirements. The prequalification of diagnostics process includes three main components: • review of an application form and product dossier; • laboratory evaluation of the product; and • inspection of the manufacturing site(s). Another element of the WHO Prequalification of Diagnostics Programme is the strengthening of the regulatory capacity of WHO Member States to improve pre- and post-market regulatory oversight of diagnostics. The findings of the WHO Prequalification of Diagnostics Programme are used to provide technical information principally to other United Nations (UN) agencies, but also to WHO Member States and other interested organizations, on particular diagnostic technologies. The prequalification status of diagnostics, in conjunction with other procurement criteria, is used by UN agencies, WHO Member States and other interested organizations to guide their procurement of diagnostics. Prequalification does not imply any approval by WHO of the diagnostic products and manufacturing site(s) in question (which is the sole prerogative of national regulatory authorities). Moreover, prequalification does not constitute any endorsement or warranty by WHO of the fitness of any product for a particular purpose, including its safety and/or efficacy in the diagnosis of specific diseases. 2. Intended Audience This document has been prepared to provide an overview of the WHO prequalification of diagnostics process for manufacturers who seek an assessment of their product(s). It is recommended that manufacturers of diagnostics wishing to apply for WHO prequalification of their product(s) read this document before starting the prequalification application process. This will ensure that they are aware of and prepared for all stages of the prequalification assessment process. Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 PQDx_007 v4 22 March 2011 4 3. Process Overview 3.1. About prequalification of diagnostics The main goal of the WHO Prequalification of Diagnostics Programme is to improve access to diagnostic technologies that are safe, affordable, of good quality and are appropriate for use in resource-limited settings. To this end, the WHO Prequalification of Diagnostics Programme provides information on the outcomes of the intermediate and final steps of the prequalification assessment process to UN agencies, WHO Member States, and other interested organizations to guide their procurement decisions. Once a diagnostic product has been prequalified, it is included in the WHO list of prequalified diagnostics and becomes eligible to be invited into the procurement processes of UN agencies. Countries and other interested organizations also use the list of prequalified products as a tool for guiding their procurement decisions. Hence, prequalification of diagnostics is a procurement- driven programme that aims to ensure cost-effective use of resources. 3.2. Eligibility for prequalification of diagnostics Applications for WHO prequalification of diagnostics are only accepted from the manufacturer of the product. The WHO Prequalification of Diagnostics Programme uses the Global Harmonization Task Force (GHTF) definition of a manufacturer: Manufacturer means any natural or legal person with responsibility for design and/or manufacture of a diagnostic product with the intention of making the diagnostic product available for use, under his/her name; whether or not such a diagnostic product is designed and/or manufactured by that person himself/herself or on his/her behalf by another person(s). 1 3.3. "Re-branding" arrangements WHO is aware that that certain companies purchase finalized products from other manufacturers and then "re-brand" these products. WHO considers a "re-branded" product to be one that is manufactured under identical conditions at the same manufacturing site(s) as the original product. In other words, a “re-branded” product is identical in every aspect to the product manufactured by the original manufacturer, except that the product is labeled with a "re-branded" product name and identifier. WHO encourages joint applications by original manufacturers and "re-branders". Prequalification of diagnostics applications for "re-branded" products will be considered based on the prioritization criteria. 1 This definition for manufacturer is based on definitions used by the Global Harmonization Task Force (GHTF). The GHTF is a voluntary group of representatives from national medical device regulatory authorities and the regulated industry and was formed to encourage convergence in regulatory practices. This internationally accepted approach of defining a manufacturer has been adopted to ensure that there is a clear understanding of the term "manufacturer" across international markets. For further details visit the following website: http://www.ghtf.org/documents/ Administrator 高亮 PQDx_007 v4 22 March 2011 5 A condition for the prequalification assessment of a "re-branded" product is that the original product manufacturer and the "re-brander" explicitly consent to the public disclosure by WHO of this "re-branding" arrangement. 3.4. Prioritization criteria for the review of applications In order to meet the needs of WHO Member States and UN agencies, conditions for prioritization of the review of applications for prequalification of diagnostics have been established, which take into account a number of aspects such as: • the need for diagnostic technologies for a particular disease or disease state; • the appropriateness of the product for use in resource-limited settings; • the requests from WHO Member States for particular diagnostic products; • the performance capabilities of particular diagnostic technologies; and/or • the availability of currently prequalified products that are similar or the same. Although all applications received from manufacturers will be reviewed in accordance with this procedure, those products meeting the prioritization criteria will be given priority. The prioritization criteria are periodically reviewed and made publicly available by WHO. This is done in consultation with other UN agencies and with experts in particular disease areas and diagnostic technologies. WHO also obtains input from WHO Member States to determine which diagnostic technologies are of priority to them. 3.5. Readiness for prequalification To ensure that WHO can prequalify diagnostics as efficiently as possible, it is expected that manufacturers will be fully prepared for prequalification before submitting the product dossier. WHO reserves the right to terminate the prequalification assessment process at any time/stage if the manufacturer is not able to, or fails to, provide the required information, and/or the manufacturer is unable to implement any corrective actions which WHO may require in a specified time period, or when the information supplied is inadequate for effective prequalification assessment. In this case, the manufacturer will not be eligible to re-apply for WHO prequalification assessment for one year from the date of the notification of termination. 3.6. Components of the prequalification of diagnostics assessment process The prequalification of diagnostics process includes three main components: • review of an application form and product dossier • laboratory evaluation of the product and • inspection of the manufacturing site(s). Figure 1 depicts the way in which the prequalification of diagnostics process proceeds through the particular assessment stages. Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 HJD Notes Be Careful Not To Be Terminated By WHO！！！ PQDx_007 v4 22 March 2011 6 WHO recognizes the assessment of relevant products by national regulatory authorities which apply stringent standards for quality, similar to those applied by WHO. Provided that the national regulatory authorities and holders of the regulatory approvals of diagnostic products submitted for WHO prequalification are willing to share certain information with WHO on the product(s) in question, WHO may consider in the WHO prequalification assessment process all or part of the findings of the scientific assessment and inspections conducted by the regulatory authority concerned. 4. Review of an Application Form and Product Dossier 4.1. Application form submission Submission of the completed application form is the first step in the prequalification assessment process. This completed application form provides summary information about the diagnostic product and the manufacturer. The manufacturer should complete the application form and provide all requested information as prescribed by the document "Instructions for the Completion of the Application Form". WHO reviews the application form to determine whether it is complete (applications that are incomplete will not be considered) and whether the manufacturer uses a quality management system with respect to the submitted product. If that is the case, the manufacturer is notified that Manufacturer submits application Accepted Rejected Application is screened Manufacturer signs letter of agreement, pays fee and submits product dossier Dossier is reviewed Accepted Rejected Manufacturing Site Inspection Meets WHO requirements Does not meet WHO requirements Meets WHO requirements Does not meet WHO requirements Product is prequalified Product Laboratory Evaluation Post-market surveillance Figure 1: Overview of the prequalification of diagnostics process Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 线条 Administrator 矩形 Administrator 高亮 Administrator 高亮 PQDx_007 v4 22 March 2011 7 the product is ready to proceed further in the assessment process2 and a formal Letter of Agreement is subsequently sent to him by WHO. The Letter of Agreement is to be duly signed and sent back to WHO and a non-refundable prequalification assessment fee levied before the process can proceed further. Upon completion of these requirements, the manufacturer will receive an invitation to submit a product dossier. 4.2. Product dossier submission The diagnostic product will only proceed to the product dossier review stage if and when WHO formally invites the manufacturer to submit a product dossier. The manufacturer should compile and submit the product dossier as prescribed by the document "Instructions for Compilation of a Product Dossier". Furthermore, the product dossier should be submitted using the document "Product Dossier Checklist" as the first page. All sections of the dossier should be cross-referenced to this first page. The content of the product dossier should be consistent with the information submitted in the application form. Once the product dossier has been received by WHO, it is screened for completeness and provided it contains all the required information, it undergoes a full review. If the product dossier is incomplete, the manufacturer will be informed that an incomplete product dossier has been received and will be requested to complete it within a specified time period. In the event of non-compliance, the product dossier will be rejected on grounds of incompleteness and the prequalification process will be terminated. The information submitted in the product dossier will be reviewed by WHO staff and external experts (assessors) appointed by WHO. The assessors will act as temporary advisers to WHO. They must have the qualifications and experience in the relevant fields and must comply with the confidentiality and conflict of interests rules of WHO. The assessment of product dossiers will be done in accordance with an SOP established by WHO for that purpose so as to ensure uniformity in the conducted review and timeliness of assessment activities. In the event that a diagnostic product has received a recent valid regulatory approval from a stringent regulatory authority and both the holder and provider of the approval are willing to share certain information related to the approval with WHO, a fast track assessment procedure, as defined in a specific SOP established by WHO, may be applied. The findings from the product dossier assessment including, but not limited to, deficiencies of the documentation and data submitted, shall be communicated in writing to the applicant, requesting submission of the missing data and information, as appropriate. The decision to continue the prequalification assessment process is based on the successful review of the product dossier content. Acceptable dossiers will proceed to the laboratory evaluation and/or manufacturing site(s) inspection stages. NOTE: Manufacturers should not submit a product dossier or pay the prequalification assessment fee unless instructed to do so by WHO. The product dossier will otherwise be returned to the manufacturer without review. 2 As mentioned under section 3.4 above, those products meeting one or more of the prioritization criteria will be given priority. Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 PQDx_007 v4 22 March 2011 8 5. Laboratory Evaluation of the Product Laboratory evaluation of the product will occur following a successful review of the product dossier. The purpose of the laboratory evaluation is to assess the operational and performance characteristics of the product and is carried out by specified WHO Collaborating Centre(s) 3 under the instructions of WHO. The product will be evaluated against preset performance criteria as described in the relevant WHO Technical Working group of experts meeting reports and in any update or revision thereof. Before commencement of the laboratory evaluation, the evaluation protocol will be forwarded to the manufacturer. The protocol outlines the procedures used to evaluate the product performance and operational characteristics. The number of tests required for the laboratory evaluation will depend on the product/analyte under evaluation. Only upon instruction of WHO, the manufacturer will be contacted by the relevant WHO Collaborating Centre(s) and requested to provide sufficient quantities of diagnostic tests and, if required, equipment to perform the laboratory evaluation. NOTE: The manufacturer should not send di